This application requests continued funding to support a second follow-up of children of mothers with drug abuse and other commonly co-occurring disorders. At baseline (or Time1), we assessed maladjustment, competence, and risk and protective factors in a sample of 360 eight to seventeen year old children and their mothers; about half of the mothers had diagnoses of cocaine/opioid dependence or abuse. At the first follow-up (Time 2), the children were 12-21 years old; at the time of submitting this application, we have completed 579 of 720 Time 2 assessments with a projected retention rate of at least 90 percent. In the proposed project (Time 3), we seek to re- assess this cohort about 4 years after their last assessment, when the offspring will be 18-25 years old, a time of high risk for substance abuse and conduct problems. Specific aims are (1) to determine whether maternal drug abuse, versus affective/anxiety diagnoses, is linked with significant offspring pathology during adulthood; (2) To examine mechanisms underlying links between maternal and offspring disorder and vulnerability/protective factors, involving (i) enduring aspects of maternal functioning (personality disturbances, ego development, and negative parenting behaviors); (ii) genetic vulnerability factors (polymorphisms of the CNS dopaminergic pathway); (iii) offspring stress-reactivity (via cortisol levels and vagal tone),deficits in executive control, and personality disturbances; (iv) supportiveness versus deviance in offsprings' close personal relationships. (3) To examine the degree to which offsprings' psychopathology might presage increases in mothers' stress and distress over time. Prior waves entailed measurement of diverse risk and protective indices via multiple methods and informants, with offspring outcomes assessed in terms of diagnostic and dimensional maladjustment as well as competence across stage-salient developmental tasks. In this new follow-up, we will continue comprehensive psychiatric and behavioral assessments and supplement these with biological and genetic ones. This will be among the first studies to obtain this breadth of prospective assessments on a large cohort of offspring of addicted mothers, with matched samples of children of (a) mothers with affective/ anxiety disorders and (b) none of these diagnoses. Data from our first 2 assessments show that children of drug abusing mothers did not fare more poorly than SES matched others through adolescence. At the same time, there are signs of significant problems (e.g., antisocial problems) potentially emerging around adulthood. Building on in-depth prospective data in this high-risk group followed from late childhood/ adolescence through early adulthood, insights from this study could be highly significant in contributing to developmental psychopathology theory and research, and in informing translational efforts involving expedient interventions and social policies to benefit an extremely vulnerable population of today's children and families. Cocaine/heroin abusing mothers are widely viewed as highly destructive for their minor children, but this ongoing study has shown that up through adolescence, their children are at no greater risk for adjustment problems than are children of depressed/anxious women. By early adulthood, however, addicted mothers' children do begin to show some antisocial problems. Building on data from 8 years in the past, continued assessments of these youth will clarify risks linked with different maternal mental illnesses as well as protective factors that allow some children to do well, even through adulthood, while others falter. Preventive interventions guided by these data could result in great savings to the legal, educational, and health care systems in contemporary society.